The present invention relates to compounds which are useful for inhibiting protein kinases, methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
Protein kinases have been clearly shown to be important in the progression of many disease states that are induced by the inappropriate proliferation of cells. These kinases are often found to be up-regulated in many hyperproliferative states such as cancer. These kinases may be important in cell signaling, where their inappropriate activation induces cells to proliferate (e.g. EGFR, ERBB2, VEGFR, FGFR, PDGFR, c-Met, IGF-1R, RET, TIE2). Alternatively, they may be involved in signal transduction within cells (e.g. c-Src, PKC, Akt, PKA, c-Ab1, PDK-1). Often these signal transduction genes are recognized proto-oncogenes. Many of these kinases control cell cycle progression near the G1-S transition (e.g. Cdk2, Cdk4), at the G2-M transition (e.g. Wee1, Myt1, Chk1, Cdc2) or at the spindle checkpoint (Plk, Aurora1 or 2, Bub1 or 3). Furthermore, kinases are intimately linked to the DNA damage response (e.g. ATM, ATR, Chk1, Chk2). Disregulation of these cellular functions; cell signaling, signal transduction, cell cycle control, and DNA repair, are all hallmarks of hyperproliferative diseases, particularly cancer. It is therefore likely that pharmacological modulation of one or more kinases would be useful in slowing or stopping disease progression in these diseases.
In its principle embodiment the present invention provides a compound of formula (I) 
or a therapeutically acceptable salt thereof, wherein
X is selected from the group consisting of C(R8) and N; wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido;
Xxe2x80x2 is selected from the group consisting of C and N;
Y is selected from the group consisting of C and N;
Yxe2x80x2 is selected from the group consisting of C(R9) and N; wherein R9 is selected from the group consisting of hydrogen and -L2-L3(R3)(R6);
Z is selected from the group consisting of C and N;
provided that 0, 1, or 2 of X, Xxe2x80x2, Y, Yxe2x80x2, and Z are N;
L1 is selected from the group consisting of a bond, xe2x80x94Oxe2x80x94, xe2x80x94NR5xe2x80x94, alkenyl, alkynyl, xe2x80x94C(O)xe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(O)xe2x80x94, xe2x80x94S(O)2xe2x80x94, xe2x80x94S(O)2N(R5)xe2x80x94, xe2x80x94N(R5)S(O)2xe2x80x94, xe2x80x94C(R12)2xe2x80x94, xe2x80x94C(R12)2N(R5)xe2x80x94, xe2x80x94N(R5)C(O)xe2x80x94, and xe2x80x94C(O)N(R5)xe2x80x94; wherein each group is drawn with its left end attached to R1 and its right end attached to the aromatic ring;
L2 is selected from the group consisting of a bond, xe2x80x94Oxe2x80x94, xe2x80x94C(R12)2xe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94N(R5)xe2x80x94, xe2x80x94N(R5)C(O)xe2x80x94, and xe2x80x94C(O)N(R5)xe2x80x94;
L3 is selected from the group consisting of a bond, alkylidene and alkylene, wherein the alkylidene and the alkylene are optionally substituted with one or two substituents independently selected from the group consisting of alkoxy, amino, cyano, and hydroxy;
R1 is selected from the group consisting of aryl, heteroaryl, and heterocycle;
R2 and R4 are independently absent or selected from the group consisting of hydrogen, alkenyl, alkyl, alkynyl, amino, aryl, arylalkynyl, cyano, cyanoalkenyl, halo, heteroaryl, heterocycle, hydroxyalkyl, and nitro; or
R2 and L1, together with the carbon atoms to which they are attached, form a ring selected from the group consisting of aryl, heteroaryl, and heterocycle; or
R4 and L2, together with the carbon atoms to which they are attached, form a ring selected from the group consisting of aryl, heteroaryl, and heterocycle;
provided that when L3 is alkylidene, R4 and L2, together with the carbon atoms to which they are attached, form a ring selected from the group consisting of aryl, heteroaryl, and heterocycle;
R3 is absent or selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle;
R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle;
provided that when L1 and L2 are bonds, at least one of R3 and R6 is other than hydrogen;
R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl;
R7 is absent or selected from the group consisting of hydrogen, alkyl, cyanoalkenyl, and -L2-L3(R3)(R6); or
R7 and L1, together with the carbon atoms to which they are attached, form a ring selected from the group consisting of aryl, heteroaryl, and heterocycle; and
each R12 is selected from the group consisting of hydrogen, alkenyl, alkyl, alkynyl, amino, aryl, cyano, halo, heteroaryl, heterocycle, and nitro.
In another embodiment the present invention provides a compound of formula (II) 
or a therapeutically acceptable salt thereof, wherein
L1 is selected from the group consisting of a bond, xe2x80x94Oxe2x80x94, xe2x80x94N(R5)xe2x80x94, alkenyl, alkynyl, xe2x80x94N(R5)C(O)xe2x80x94, and xe2x80x94C(O)N(R5)xe2x80x94;
L2 is selected from the group consisting of a bond, xe2x80x94Oxe2x80x94, xe2x80x94N(R5)xe2x80x94, xe2x80x94N(R5)C(O)xe2x80x94, and xe2x80x94C(O)N(R5)xe2x80x94;
L3 is selected from the group consisting of a bond, alkylidene, and alkylene, wherein the alkylidene and the alkylene are optionally substituted with one or two substituents independently selected from the group consisting of amino, cyano, and hydroxy;
R1 is selected from the group consisting of aryl, heteroaryl, and heterocycle;
R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl; wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; or
R2 and L1, together with the carbon atoms to which they are attached, form a ring selected from the group consisting of dihydropyrrolyl, pyrazolyl, and phenyl; or
R4 and L2, together with the carbon atoms to which they are attached, form a ring selected from the group consisting of dihydropyrrolyl, phenyl, pyridinyl, and pyrrolyl; wherein the ring can be optionally substituted with oxo; provided that when L3 is alkylidene, R4 and L2, together with the carbon atoms to which they are attached, form a ring selected from the group consisting of dihydropyrrolyl, phenyl, pyridinyl, and pyrrolyl; wherein the ring can be optionally substituted with oxo;
R3 is absent or selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle;
R6 are independently selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, and heteroarylalkoxy, heteroaryloxy, and heterocycle;
provided that when L1 and L2 are bonds, at least one of R3 and R6 is other than hydrogen;
R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; and
X is selected from the group consisting of C(R8) and N; wherein R8 is selected from the group consisting of hydrogen, amino, carboxy, cyano, and halo.
In another embodiment the present invention provides a compound of formula (III) 
or a therapeutically acceptable salt thereof, wherein
L1 is selected from the group consisting of a bond, xe2x80x94Oxe2x80x94, xe2x80x94N(R5)xe2x80x94, alkenyl, alkynyl, and xe2x80x94N(R5)C(O)xe2x80x94;
L2 is selected from the group consisting of a bond, xe2x80x94Oxe2x80x94, xe2x80x94N(R5)xe2x80x94, xe2x80x94N(R5)C(O)xe2x80x94, and xe2x80x94C(O)N(R5)xe2x80x94;
L3 is alkylene, wherein the alkylene is substituted with one or two substituents independently selected from the group consisting of amino and hydroxy;
R1 is selected from the group consisting of aryl, heteroaryl, and heterocycle;
R2 and R4 are independently selected from the group consisting of hydrogen and halo;
R3 and R6 are independently selected from the group consisting of hydrogen, aryl, arylalkoxy, and heteroaryl; provided that when L1 and L2 are bonds, at least one of R3 and R6 is other than hydrogen; and
R5 is selected from the group consisting of hydrogen and alkyl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is alkenyl; L2 is selected from the group consisting of a bond, xe2x80x94Oxe2x80x94, xe2x80x94C(R12)2xe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94N(R5)xe2x80x94, xe2x80x94N(R5)C(O)xe2x80x94, and xe2x80x94C(O)N(R5)xe2x80x94; L3 is a bond or selected from the group consisting of alkylidene and alkylene, wherein the alkylidene and the alkylene are optionally substituted with one or two substituents independently selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heteroaryl, and heterocycle; R2 and R4 are independently absent or selected from the group consisting of hydrogen, alkenyl, alkyl, alkynyl, amino, aryl, arylalkynyl, cyano, cyanoalkenyl, halo, heteroaryl, heterocycle, hydroxyalkyl, and nitro; R3 is absent or selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl; and each R12 is selected from the group consisting of hydrogen, alkenyl, alkyl, alkynyl, amino, aryl, cyano, halo, heteroaryl, heterocycle, and nitro.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is alkenyl; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heterocycle, and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; and R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is alkenyl; L2 is xe2x80x94Oxe2x80x94; L1 is alkenyl; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; and R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is alkenyl; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is heteroaryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; and Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is alkenyl; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is aryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; and Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is alkenyl; L2 is xe2x80x94Oxe2x80x94; L3 is a bond; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is absent; R6 is heterocycle; and R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is alkenyl; L2 is xe2x80x94Oxe2x80x94; L3 is a bond; R1 is heteroaryl; R2 and R4 are hydrogen; R3 is absent; R6 is heterocycle; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is alkenyl; L2 is xe2x80x94N(R5)C(O)xe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heterocycle, and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; and R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; and Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is alkenyl; L2 is xe2x80x94N(R5)C(O)xe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is heteroaryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is alkenyl; L2 is xe2x80x94N(R5)C(O)xe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is aryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is alkynyl; L2 is selected from the group consisting of a bond, xe2x80x94Oxe2x80x94, xe2x80x94C(R12)2xe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94N(R5)xe2x80x94, xe2x80x94N(R5)C(O)xe2x80x94, and xe2x80x94C(O)N(R5)xe2x80x94; L3 is a bond or selected from the group consisting of alkylidene and alkylene, wherein the alkylidene and the alkylene are optionally substituted with one or two substituents independently selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heteroaryl, and heterocycle; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkyl, alkynyl, amino, aryl, arylalkynyl, cyano, cyanoalkenyl, halo, heteroaryl, heterocycle, hydroxyalkyl, and nitro; R3 is absent or selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl; and each R12 is selected from the group consisting of hydrogen, alkenyl, alkyl, alkynyl, amino, aryl, cyano, halo, heteroaryl, heterocycle, and nitro.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is alkynyl; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heterocycle, and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; and R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is selected from the group consisting of a bond, xe2x80x94Oxe2x80x94, xe2x80x94C(R12)2xe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94N(R5)xe2x80x94, xe2x80x94N(R5)C(O)xe2x80x94, and xe2x80x94C(O)N(R5)xe2x80x94; L3 is a bond or selected from the group consisting of alkylidene and alkylene, wherein the alkylidene and the alkylene are optionally substituted with one or two substituents independently selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heteroaryl, and heterocycle; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkyl, alkynyl, amino, aryl, arylalkynyl, cyano, cyanoalkenyl, halo, heteroaryl, heterocycle, hydroxyalkyl, and nitro; R3 is absent or selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl; and each R12 is selected from the group consisting of hydrogen, alkenyl, alkyl, alkynyl, amino, aryl, cyano, halo, heteroaryl, heterocycle, and nitro.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; and Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heterocycle, and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; and R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is aryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is heteroaryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is hydrogen; Xxe2x80x2 is N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is heteroaryl; and R7 is absent.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is N; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 is absent; R4 is selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is aryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is N; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 is absent; R4 is selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is heteroaryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is C(R8), wherein R8 is hydrogen; Xxe2x80x2 is C; Y is N; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 is absent; R4 is selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is aryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is C(R8), wherein R8 is hydrogen; Xxe2x80x2 is C; Y is N; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 is absent; R4 is selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is heteroaryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is C(R8), wherein R8 is hydrogen; Xxe2x80x2 is C; Y is N; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is N; L1 is a bond; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R4 is absent; R2 is selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is aryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is C(R8), wherein R8 is hydrogen; Xxe2x80x2 is C; Y is N; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is N; L1 is a bond; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R4 is absent; R2 is selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is heteroaryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is N; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is N; L1 is a bond; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R4 is absent; R2 is selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is aryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is N; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is N; L1 is a bond; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R4 is absent; R2 is selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is heteroaryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is xe2x80x94Cxe2x80x94; L1 is a bond; L2 is xe2x80x94N(R5)xe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heterocycle, and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; and R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is xe2x80x94N(R5)xe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R6 is heteroaryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is xe2x80x94N(R5)xe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R6 is aryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is xe2x80x94N(R5)C(O)xe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heterocycle, and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; and R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is xe2x80x94N(R5)C(O)xe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is heteroaryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is xe2x80x94N(R5)C(O)xe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R6 is aryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is xe2x80x94N(R5)xe2x80x94; L2 is selected from the group consisting of a bond, xe2x80x94Oxe2x80x94, xe2x80x94C(R12)2xe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94N(R5)xe2x80x94, xe2x80x94N(R5)C(O)xe2x80x94, and xe2x80x94C(O)N(R5)xe2x80x94; L3 is a bond or selected from the group consisting of alkylidene and alkylene, wherein the alkylidene and the alkylene are optionally substituted with one or two substituents independently selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heteroaryl, and heterocycle; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkyl, alkynyl, amino, aryl, arylalkynyl, cyano, cyanoalkenyl, halo, heteroaryl, heterocycle, hydroxyalkyl, and nitro; R3 is absent or selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl; and each R12 is selected from the group consisting of hydrogen, alkenyl, alkyl, alkynyl, amino, aryl, cyano, halo, heteroaryl, heterocycle, and nitro.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is xe2x80x94N(R5)xe2x80x94; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heterocycle, and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; and R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is xe2x80x94N(R5)xe2x80x94; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heterocycle, and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R6 is heteroaryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is xe2x80x94N(R5)xe2x80x94; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heterocycle, and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is hydrogen; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R6 is aryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L2 is a bond; L3 is a bond; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrazinyl, thiazolyl, and thienyl; R3 is absent; R6 is heterocycle; and R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N; wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is selected from the group consisting of a bond, xe2x80x94Oxe2x80x94, xe2x80x94N(R5)xe2x80x94, alkenyl, alkynyl, xe2x80x94C(O)xe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(O)xe2x80x94, xe2x80x94S(O)2xe2x80x94, xe2x80x94S(O)2N(R5)xe2x80x94, xe2x80x94N(R5)S(O)2xe2x80x94, xe2x80x94C(R12)2xe2x80x94, xe2x80x94C(R12)2N(R5)xe2x80x94, xe2x80x94N(R5)C(O)xe2x80x94, and xe2x80x94C(O)N(R5)xe2x80x94, wherein each group is drawn with its left end attached to R1 and its right end attached to the aromatic ring; L3 is alkylidene, wherein the alkylidene is optionally substituted with one or two substituents independently selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heteroaryl, and heterocycle; R4 and L2, together with the carbon atoms to which they are attached, form a ring selected from the group consisting of aryl, heteroaryl, and heterocycle; R3 is absent or selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, arylalkylamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocycle; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl; and each R12 is selected from the group consisting of hydrogen, alkenyl, alkyl, alkynyl, amino, aryl, cyano, halo, heteroaryl, heterocycle, and nitro.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N, wherein R8 is hydrogen; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; L1 is a bond; L3 is alkylidene, wherein the alkylidene is substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl wherein the heteroaryl is isoquinolinyl; R4 and L2, together with the carbon atoms to which they are attached, form a heterocycle wherein the heterocycle is pyrrolidinyl substituted with oxo; R3 is hydrogen; R6 is heteroaryl, wherein the heteroaryl is indolyl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N; wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; and Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; R2 and L1, together with the carbon atoms to which they are attached, form a ring that is aryl wherein the aryl ring is phenyl; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R3 is absent; R6 is heteroaryl; and R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; R2 and L1, together with the carbon atoms to which they are attached, form a ring that is aryl wherein the aryl ring is phenyl; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R3 is absent; R6 is heteroaryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; R2 and L1, together with the carbon atoms to which they are attached, form a ring that is aryl wherein the aryl ring is phenyl; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R3 is absent; R6 is aryl; and R7 is hydrogen.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N; wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; Xxe2x80x2 is selected from the group consisting of C and N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; R2 and L1, together with the carbon atoms to which they are attached, form a ring that is heteroaryl wherein the heteroaryl is pyrazolyl; L2 is a bond; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heterocycle, and heteroaryl; R3 is hydrogen; R6 is selected from the group consisting of aryl, heterocycle, and heteroaryl; and R7 is absent or selected from the group consisting of hydrogen, alkyl, and cyanoalkenyl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is C(R8), wherein R8 is hydrogen; Xxe2x80x2 is N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; R2 and L1, together with the carbon atoms to which they are attached, form a ring that is heteroaryl wherein the heteroaryl is pyrazolyl; L2 is a bond; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R3 is hydrogen; R6 is aryl; and R7 is absent.
In another embodiment, the present invention provides a compound of formula (I) wherein X is C(R8), wherein R8 is hydrogen; Xxe2x80x2 is N; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; R2 and L1, together with the carbon atoms to which they are attached, form a ring that is heteroaryl wherein the heteroaryl is pyrazolyl; L2 is a bond; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is aryl; R3 is hydrogen; R6 is aryl; and R7 is absent.
In another embodiment, the present invention provides a compound of formula (I) wherein X is selected from the group consisting of C(R8) and N; wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, carboxy, cyano, halo, hydroxy, and amido; X is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; R7 and L1, together with the carbon atoms to which they are attached, form a ring selected from the group consisting aryl, heteroaryl and heterocycle; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is selected from the group consisting of aryl, heterocycle, and heteroaryl; R3 is hydrogen; and R6 is selected from the group consisting of aryl, heterocycle, and heteroaryl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; and Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; R7 and L1, together with the carbon atoms to which they are attached, form a ring that is a heteroaryl wherein the heteroaryl is pyridinyl; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R3 is hydrogen; and R6 is heteroaryl.
In another embodiment, the present invention provides a compound of formula (I) wherein X is N; and Xxe2x80x2 is C; Y is C; Yxe2x80x2 is C(R9), wherein R9 is -L2-L3(R3)(R6); Z is C; R7 and L1, together with the carbon atoms to which they are attached, form a ring that is a heteroaryl wherein the heteroaryl is pyridinyl; L2 is xe2x80x94Oxe2x80x94; L3 is alkylene, wherein the alkylene is optionally substituted with one substituent selected from the group consisting of alkoxy, amino, cyano, and hydroxy; R1 is heteroaryl; R3 is hydrogen; and R6 is aryl.
In another embodiment the invention provides a pharmaceutical composition comprising a compound of formula (I), or a therapeutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
In another embodiment the invention provides a method of inhibiting protein kinases in a patient in recognized need of such treatment comprising administering to the patient a therapeutically acceptable amount of a compound of formula (I), or a therapeutically acceptable salt thereof.